Removable transmucosal elements

Abstract

The present invention relates to a dental implant healing improver (healing improver) for use in improving healing of a dental implant in an implant site, wherein said improving healing comprises (a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time; (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby (c) improving healing of said dental implant. The present invention further relates to a method for testing a mucosal tolerability of a composition of matter in a subject having at least one dental implant in an implant site, said method comprising (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period; (bb) examining the implant site after said time period; and, thereby, (cc) testing said mucosal tolerability of said composition of matter, wherein said subject is an experimental animal and wherein said method comprises further step (dd) sacrificing said experimental animal; and to kits and dental implants related thereto.

Description

[0001] Removable transmucosal elements

[0002] The present invention relates to a dental implant healing improver (healing improver) for use in improving healing of a dental implant in an implant site, wherein said improving healing comprises (a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time; (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby (c) improving healing of said dental implant. The present invention further relates to a method for testing a mucosal tolerability of a composition of matter in a subject having at least one dental implant in an implant site, said method comprising (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period; (bb) examining the implant site after said time period; and, thereby, (cc) testing said mucosal tolerability of said composition of matter, wherein said subject is an experimental animal and wherein said method comprises further step (dd) sacrificing said experimental animal; and to kits and dental implants related thereto.

[0003] Dental implants are an important option in oral rehabilitation. Typically, dental implants comprise a bone-integral part, also known as enossal or osseous portion, anchoring the implant in the jawbone of the patient and a transmucosal portion spanning the peri-implant mucosa. Said parts of the implant may be combined in one single implant part and intended for transmucosal healing (1-step healing, tissue-level implant), or may be embodied in two or more parts; in the case of two- or more piece implants (bone-level implant), typically the osseous part is separate from other components and intended for submerged healing (2-step healing), whereas the transmucosal portion and the crown may be separate parts or may be combined. In any case, the replacement of the visible part of the tooth, the crown, will be fixed onto the transmucosal portion. It is an advantage of two- or more-piece implants that the transmucosal portion may be changed while leaving the enossal portion in place. Thus, in two- or more-piece embodiments, the transmucosal component may be embodied as a mucosal former or as a healing cap, also termed "healing abutment", or as an abutment carrying the crown. Prefabricated abutments can be produced from a variety of different materials or alloys; they ensure the fixation of the artificial crown and the connection of the crown to the intraosseous implant portion. The evolution of computer aided design (CAD) and computer assisted milling (CAM, CAD / CAM) favored the creation of titanium base abutments (TBA) for various implant brands (Chantier et al. (2023), Clin Oral Implants Res 34 Suppl 26: 64). These abutments are associated with a digital library for manufacturing the fixed dental prostheses. In general, the abutments are available in a variety of transmucosal heights, which are selected according to the site-specific mucosal height and the desired clinical emergence profile. The selection of the prefabricated abutment is conducted so that the shoulder and the future crown margin is located sufficiently distanced from the bone and in a submucosal position with sufficient space for an optimal emergence profile (Derksen et al. (2023), Clin Oral Implants Res 34 Suppl 26: 104). Further, the abutment serves for static connection between the artificial crown and the intraosseous implant portion and for force transmission. The abutment is connected to the intraosseous implant portion by an abutment screw, which facilitates screw-retention of the crown and retrievability.

[0004] A common problem of dental implants is the formation of a, mostly bacterial, biofilm on the abutment or crown surface along the mucosal margin. This biofilm is barely accessible to mechanical removal with a toothbrush, and frequently is the cause of inflammatory processes leading to peri-implant mucositis, which generally is reversible after appropriate treatment, or to peri-implantitis (Berglundh et al, (2011), J Clin Periodontol 38 Suppl 11 : 188). Peri-implant mucositis has been estimated to occur in 63% of patients carrying dental implants, and at 31% of dental implants installed. What is more, peri-implantitis is diagnosed in 19% of dental implant patients and at 10% of dental implants installed (Atieh et al. (2013), J Periodontol 84: 1586 Untreated peri-implantitis can lead to bone defects and to loss of the implant.

[0005] Besides inflammatory processes, also initial healing of a dental implant site and maintenance of an implant site in a healthy state depends on a variety of factors, which may be mutually dependent, such as oral hygiene, oral microflora, eating habits, smoking habits, and the like. However, also the material and structure of material in contact with living tissue such as the peri-implant mucosa, were found to be important factors influencing dental implant health (Ferraris et al. (2017), Materials Science Engineering C76: 1). There is, thus, a need in the art for improved means and methods for identifying and providing suitable dental implants, in particular transmucosal portions thereof. Such improved means and methods are provided by the embodiments of the present invention.

[0006] In accordance, the present invention relates to a dental implant healing improver (healing improver) for use in improving healing of a dental implant in an implant site, wherein said improving healing comprises

[0007] (a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time;

[0008] (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby

[0009] (c) improving healing of said dental implant.

[0010] In general, terms used herein are to be given their ordinary and customary meaning to a person of ordinary skill in the art and, unless indicated otherwise, are not to be limited to a special or customized meaning. As used in the following, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements. Also, as is understood by the skilled person, the expressions "comprising a" and "comprising an" preferably refer to "comprising one or more", i.e. are equivalent to "comprising at least one". In accordance, expressions relating to one item of a plurality, unless otherwise indicated, preferably relate to at least one such item, more preferably a plurality thereof; thus, e.g. providing "a subject" relates to providing at least one subject, preferably to providing a multitude of subjects.

[0011] Further, as used in the following, the terms "preferably", "more preferably", "most preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting further possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment" or similar expressions are intended to be optional features, without any restriction regarding further embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.

[0012] The methods specified herein below, preferably, are in vitro methods; in particular methods of treatment and other methods performed on the body of a subject may, however, also be performed in vivo. The method steps may, in principle, be performed in any arbitrary sequence deemed suitable by the skilled person, but preferably are performed in the indicated sequence; also, one or more, preferably all, of said steps may be assisted or performed by automated equipment. Moreover, the methods may comprise steps in addition to those explicitly mentioned above.

[0013] As used herein, if not otherwise indicated, the term "about" relates to the indicated value with the commonly accepted technical precision in the relevant field, preferably relates to the indicated value ± 20%, more preferably ± 10%, most preferably ± 5%. Further, the term "essentially" indicates that deviations having influence on the indicated result or use are absent, i.e. potential deviations do not cause the indicated result to deviate by more than ± 20%, more preferably ± 10%, most preferably ± 5%. Thus, “consisting essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention. For example, a composition defined using the phrase “consisting essentially of’ encompasses any known acceptable additive, excipient, diluent, carrier, and the like. Preferably, a composition consisting essentially of a set of components will comprise less than 5% by weight, more preferably less than 3% by weight, even more preferably less than 1% by weight, most preferably less than 0.1% by weight of non-specified component(s).

[0014] The term "dental implant" is understood by the skilled person and relates to a device anchoring a dental prosthesis, e.g. the crown of an artificial tooth, in a jawbone of a subject. As detailed herein above, dental implants may in principle be manufactured as one-piece embodiments, as two-piece embodiments, or as three or more-piece embodiments. A one-piece dental implant, preferably, comprises at least (i) an enossal portion, anchoring the dental implant in the bone, (ii) a transmucosal portion spanning the gum / mucosa, and (iii) the abutment for crown fixation. It will be understood by the skilled person that the final, complete dental restoration typically further comprises a crown replacing the visible part of the tooth in the oral cavity. In two- or more-piece embodiments, preferably, at least one of the aforesaid portions (i) to (iii) is embodied as a discrete component of the dental implant. As the skilled person will appreciate, the terms "compound" and "element" are used herein to relate to discrete tangible objects, while the term "portion" is used to relate to a portion of a compound or element, which portion may, but does not have to be, physically discernible from other portions; in particular, a portion may be defined by a function and / or a location of said portion in the implanted dental implant, e.g. as a transmucosal portion as specified herein below.

[0015] In two- or more-piece embodiments, the enossal portion is embodied as a discrete component, the enossal component. Preferably, in two- or more-piece embodiments, at least the enossal portion and the transmucosal portion are embodied as discrete component, i.e. as an enossal component and a transmucosal component, respectively. Preferably, in such a case, the enossal portion is a discrete component comprising a female screw thread, into which at least a transmucosal component can be anchored, preferably via a screw connection. Preferably, in two- or more-piece embodiments, the transmucosal component is or comprises a mucosal former, a healing cap (healing abutment), an abutment (secondary component) for fixed dental prostheses, or a retention component for removable restorations. The abutment, which may also be referred to as "abutment component", preferably, can also be integrated into the final crown restoration, so that the crown is directly connected to the osseous implant part. Accordingly, the term "dental implant or component thereof comprising a transmucosal portion", preferably, relates to a one-piece dental implant comprising a transmucosal portion; or the term relates to an component of a two- or more-piece dental implant comprising a transmucosal portion, i.e., preferably, a mucosal former, a healing cap, an abutment, a retention component or a crown as specified herein above. In a preferred embodiment, the dental implant is a long-term implant, i.e. preferably, a permanent implant; preferably, said long-term implant is implanted for at least one year, more preferably for at least five years, still more preferably for at least ten years, most preferably, for at least 20 years.

[0016] The term "transmucosal portion", as used herein, relates to a portion of a device, in particular of a dental implant or component thereof or of a transmucosal element, at least partially spanning the mucosa covering the jawbone, i.e. spanning the gum / mucosa. Accordingly, preferably, the transmucosal portion of a dental implant or component thereof is a portion spanning the section between the jawbone and the oral cavity. It is understood by the skilled person that, preferably, the transmucosal portion may extend up to 2mm, more preferably 1mm into the oral cavity. Most preferably, however, the transmucosal portion is even with the mucosal margin or ends just below this margin, i.e. does not extend into the oral cavity.

[0017] In accordance with the above, the term "transmucosal element" relates to any removable element mountable onto a dental implant, in particular onto a transmucosal portion thereof, such it at least partially contacts the peri-implant mucosa of an implant site. Thus, the transmucosal element may cover the transmucosal portion of the dental implant at least partially. Thus, the transmucosal element preferably is mounted such that it is located between the transmucosal portion of a dental implant and the peri-implant mucosa. Preferably, the transmucosal element covers at least 25%, more preferably at least 50%, even more preferably at least 75%, of the transmucosal portion of the dental implant. Most preferably, the transmucosal element covers the transmucosal portion of the dental implant completely. As the skilled person understands in view of the description herein, the transmucosal element may also cover further portions of the dental implant at least partially; e.g. the transmucosal element may extend into the oral cavity, e.g. to ease its removal. The transmucosal element may also cover, preferably partially, further portions or components of a dental implant, e.g. an enossal portion or component; e.g. following bone resorption.

[0018] The transmucosal element is removable, i.e. it is not permanently connected to the dental implant or component thereof. Thus, the transmucosal element is temporarily fixed onto the dental implant, e.g. via a push-to-fit or a snap-to fit type of mounting. Preferably, the transmucosal element is mounted on the dental implant or component thereof such that the transmucosal element fits snugly on the dental implant, in particular its transmucosal portion, preferably such that there is essentially no free space between the transmucosal element and the dental implant after mounting. In a preferred embodiment, the design of the removable transmucosal element allows its removal together with the screw-retained restoration (e.g. a crown) or after removing said restoration, preferably without the need to rotate the removable transmucosal element and preferably without the need for biopsy sampling for analysis of cell adherence. Thus, the removable transmucosal element in a preferred embodiment has a push- to-fit or a snap-to fit mounting type, allowing non-invasive retrieval of the transmucosal element, thus enabling testing a mucosal tolerability by analysing cell adherence with techniques such as qPCR assays and microscopy on the surface of the removable transmucosal element.

[0019] The transmucosal element may in principle have any shape deemed appropriate by the skilled person. Preferably, the transmucosal element is a removable ring, which may be open or closed, fitting on the dental implant, in particular its transmucosal portion. The ring may be conical or cylindrical, preferably is conical. Preferably, the transmucosal element has a low thickness, i.e. preferably a small difference between its outer diameter and its inner diameter; preferably, said thickness is at most 2mm, preferably at most 1mm, more preferably at most 0.5mm; also preferably, the thickness of the transmucosal element is at least 0.05mm, preferably at least 0.1mm, more preferably at least 0.2mm. Thus the thickness of the transmucosal element may e.g. be of from 0.05mm to 2mm, preferably of from 0.1mm to 1mm, more preferably of from 0.2mm to 0.5mm. The thickness may be constant over the height and the circumference of the transmucosal element; however, it is also envisaged that the thickness of the transmucosal element changes, e.g. increases towards the oral cavity and / or towards the enossal portion of the dental implant. Preferably, the dental implant is not adapted for use with the transmucosal element; i.e. the transmucosal element may be designed retroactively to be mountable onto a dental implant, such that the transmucosal element may also be used on an existing dental implant or component thereof for which the use of a transmucosal element was not foreseen. In such case, e.g. the form of the dental implant, in particular its transmucosal portion, may be determined and a fitting transmucosal element may be produced, e.g. by CAD methods known in principle to the skilled person. The dental implant and one or more transmucosal elements may, however, also be adapted for common use and may e.g. be provided as a kit-of-parts.

[0020] The form of the transmucosal element thus produced may replicate or essentially replicate the shape of the transmucosal portion of the dental implant; e.g. in case the transmucosal portion has an overall conical shape, the transmucosal element may e.g. be a conical ring intervening the transmucosal portion and the peri-implant mucosa, preferably with a constant thickness; an exemplary embodiment is shown in Fig. 2(A). The form of the transmucosal element thus produced may, however, also deviate from the shape of the transmucosal portion of the dental implant; e.g. on a conical transmucosal portion, a cylindrical transmucosal element and / or a transmucosal element extending onto an enossal portion may be used. Exemplary embodiments are shown in Fig. 2(B) and (C). Preferably, using a transmucosal element which extends onto an enossal portion of a dental implant, the removably mounted transmucosal element can be moved coronally by sequential turning, e.g. along a screw thread, and thereby the attached periimplant mucosa moves along with the transmucosal element in a distal direction. E.g. in case the transmucosal element has an overall conical form, this movement brings the peri-implant mucosa closer to the implant, promoting closing healing of the implant site.

[0021] The transmucosal element may be of any material deemed appropriate by the skilled person. The skilled person may select suitable materials, e.g. titanium, gold, an alloy, or plastic, in particular to be compatible with the healing improver as described herein below. The material of the transmucosal element, more preferably, is the healing improver or comprises the healing improver described herein below. The healing improver may, however, also be applied to the material of the transmucosal element, e.g. to its surface, preferably to the surface of the transmucosal element contacting the mucosa. Such application may be accomplished by any method deemed appropriate by the skilled person, e.g. by sputtering, brushing, spraying, printing, and the like, preferably causing adsorption of the healing improver to the transmucosal element. Thus, the healing improver may e.g. be comprised in an extracellular matrix coating, a peptide coating, a polysaccharide coating, or a metal coating of a transmucosal element.

[0022] The terms "first" and "second", e.g. as first and second transmucosal elements, are used herein solely to allow differentiation of two items from the same genus and do not necessarily imply a temporal relationship or preference; thus, the first transmucosal element may be applied after the second transmucosal element, however, preferably is applied before the second transmucosal element. The aforesaid terms preferably also do not imply a ranking or evaluation of transmucosal elements.

[0023] The first transmucosal element comprises a healing improver as specified herein below. The second transmucosal element may comprise the same healing improver or a different healing improver. In any case, the healing improver comprised by the first transmucosal element may also be referred to as a "first healing improver", and the healing improver comprised by the second transmucosal element may also be referred to as the "second healing improver". In view of the above, the first and second healing improver may be identical or may be non-identical; thus, the first removable transmucosal element and said second removable transmucosal element preferably have the same composition. Also, the second healing improver may comprise the same active compound as the first healing improver plus a further active compound.

[0024] A second transmucosal element comprising the same healing improver as the first transmucosal element may e.g. be used in case the healing improver is unstable in the implant site, i.e. preferably becomes inactive over time, e.g. by dissociation from the transmucosal element, by degradation, by fouling, or any other relevant process known to the skilled person. The second transmucosal element may also comprise a healing improver non-identical to the healing improver comprised by the first transmucosal element. A second healing improver nonidentical to the first healing improver may e.g. be used to adapt treatment to the individual treatment progress.

[0025] The term "implant site" is understood by the skilled person. Preferably, the term relates to a site in the oral cavity of a subject into which a dental implant or at least an enossal component thereof was placed. Preferably, the term relates to the peri-implant mucosa surrounding such a site.

[0026] In view of the above, the term "healing" of an implant site is used herein as a broad term including any improvement of the medical condition of an implant site over time. Thus, said term encompasses healing of an implant site after initial implant placement, as well as during maintenance, e.g. during cure or reduction of peri-implant diseases. Moreover, the term also includes absence of deterioration of an implant site, i.e. maintenance of a healthy (healed) state.

[0027] In concurrence with common general use of the terms, "healing" relates to the process of health improvement, which may include a response of a subject's body to a medical condition and / or to a treatment, while the terms "treating" and "preventing" relate to measures applied to the body of a subject undertaken to re-establish or preserve a healthy state, respectively. As the skilled person understands, the process and measures may occur at the same time, i.e. e.g. a treatment as specified herein may augment healing.

[0028] The term “treating”, as used herein, refers to ameliorating the diseases or disorders referred to herein or the symptoms accompanied therewith to a significant extent. Said treating as used herein also includes an entire restoration of health with respect to the diseases or disorders referred to herein, preferably healing of a dental implant site as specified herein above. It is to be understood that treating as used in accordance with the present invention may not be effective in all subjects to be treated. However, the term shall require that preferably a statistically significant portion of subjects suffering from a disease or disorder referred to herein can be successfully treated. Whether a portion is statistically significant can be determined without further ado by the person skilled in the art using various well known statistic evaluation tools, e.g., determination of confidence intervals, p-value determination, Student's t-te st, Mann- Whitney test etc. Preferred confidence intervals are at least 90%, at least 95%, at least 97%, at least 98% or at least 99 %. The levels of significance are, preferably, set to alpha 0.1, 0.05, 0.01, 0.005, or 0.0001. Preferably, the treatment shall be effective for at least 60%, at least 70%, at least 80%, or at least 90% of the subjects of a given cohort or population.

[0029] The term “preventing” a disease or disorder refers to retaining health with respect to the diseases or disorders referred to herein for a certain period of time in a subject. It will be understood that the said period of time may be dependent on the amount of the healing improver which has been administered and individual factors of the subject discussed elsewhere herein. It is to be understood that prevention may not be effective in all subjects treated with the compound according to the present invention. However, the term requires that, preferably, a statistically significant portion of subjects of a cohort or population are effectively prevented from suffering from a disease or disorder referred to herein or its accompanying symptoms. Preferably, a cohort or population of subjects is envisaged in this context which normally, i.e. without preventive measures according to the present invention, would develop a disease or disorder as referred to herein. Whether a portion is statistically significant can be determined without further ado by the person skilled in the art using various well known statistic evaluation tools discussed elsewhere in this specification. As referred to herein, preventing preferably includes all measures for maintaining an implant site in a healthy state, in particular including e.g. identifying and / or selecting a composition of the dental implant and its transmucosal portion compatible with a particular subject and / or a particular implantation technique; and / or identifying and preferably applying an optimal design of a transmucosal portion of a dental implant, as specified herein below.

[0030] In accordance with the above, the term "dental implant healing improver", which may also be abbreviated as "healing improver", relates to any compound or composition having the biological property of improving healing of an implant site. Said improvement, preferably is an improvement of healing compared to healing observed in the absence of the healing improver. Preferably, a titanium alloy, in particular titanium aluminum niobium TieAhNb, which is the standard material used for transmucosal portions of titanium base abutments, is used as a reference for measuring improvement.

[0031] Parameters suitable for determining improvement are in principle known to the skilled person: as cohort-specific parameters, e.g. the frequency of complications, like e.g. pain, inflammation, bleeding, etc.; average duration until complete healing and / or mounting of the crown etc. may be used. As individual-specific parameters, e.g. severity and / or duration of inflammation, improvement, steadiness, or deterioration of an implant site, increased probing pocket depth, bleeding on probing, suppuration or pus, pain, etc. may be used. As referred to herein, improvement is a betterment of at least one of the aforesaid parameters; more preferably is a betterment of a multitude of the aforesaid parameters. More preferably, improvement comprises at least one of decrease of frequency of inflammation in a cohort; decrease of average duration of inflammation in a cohort; shortening of healing duration in a cohort, wherein healing duration is defined as the time from starting treatment with the healing improver or a control composition until a crown can be mounted onto the abutment. Improvement may also comprise an increase of peri-implantitis-free time after implant placement. In a preferred embodiment, a further improvement comprises an improved contacting of peri-implant tissues with the surface of the removable transmucosal element; this may be assessed by methods analysing adherence of fibroblasts, epithelial cells and / or basal lamina to the removable transmucosal element, e.g. by PCR, preferably qPCR, microscopy, mass spectrometry, and / or other methods known to the skilled person.

[0032] In the improving healing as referred to herein, at least one of the healing improvers is not a biocide, e.g. as proposed by WO 2015 / 158825 Al. Thus, in case two or more healing improvers are administered, e.g. comprised by a first and a second transmucosal element, at least one of said healing improvers preferably is not an antibacterial, antifungal, and / or antiviral compound, and is not a compound mediating immunosuppression.

[0033] Preferably, the healing improver is a dental implant attachment improver, wherein the term "dental implant attachment improver", which may also be referred to as "attachment improver", relates to each and every compound improving, preferably increasing, attachment of a periimplant mucosa to a transmucosal element and / or a transmucosal portion of a dental implant in an implant site. Said improving attachment preferably comprises inducing attachment of said peri-implant mucosa to said transmucosal element, which, after removal of the transmucosal element, improves attachment of said peri-implant mucosa to a transmucosal portion of a dental implant. As will be understood by the skilled person in view of the description herein, the attachment improver may, e.g. if found to improve attachment to a transmucosal element, be included in a transmucosal portion of a dental implant; the attachment improver may, however, also only be comprised in the transmucosal element and may cause a modification of an implant site such that the attachment improver does not have to be included in the transmucosal portion of the dental implant. Thus, the healing improver preferably is (i) a compound mediating cell adhesion, (ii) a compound inducing epigenetic changes in cells contacting said healing improver, and / or (iii) a compound or composition of a surface of said removable transmucosal element inducing adhesion of a basal lamina. Compounds mediating cell adhesion are known in the art and include in particular laminin, fibronectin, and nanoporous TiCh (Ferraris et al. (2017), Materials Science Engineering C76: 1). Compounds inducing epigenetic changes are known in the art as well and include in particular silica, bioglass, graphene and biofunctionalized nanomaterials (Larsson et al. (2018), J Biomed Mater Res B Appl Biomater 106(5):2065). The aforesaid compound or composition inducing adhesion of a basal lamina may be a metal or an alloy, preferably a silver-based alloy, in particular an alloy comprising about 12.5% (w / w) Au, about 18.9% (w / w) Pd, about 53.65% (w / w) Ag, about 14.29% (w / w) Cu, and about 0.65% (w / w) Zn to a total of 100% (w / w), an alloy which is also known under the trademark Pagalinor®2.

[0034] In view of the above, the present invention also relates to a dental implant attachment improver (attachment improver) for use in improving attachment of a peri-implant mucosa to a transmucosal portion of a dental implant in an implant site, wherein said improving attachment comprises

[0035] (A) mounting a removable transmucosal element comprising said attachment improver onto said dental implant for a period of time; and, thereby

[0036] (B) improving attachment of said peri-implant mucosa to said transmucosal portion of the dental implant in the implant site.

[0037] The term "period of time" is understood by the skilled person. For the terms "first” and "second" period of time, the above description for the terms "first" and "second" applies mutatis mutandis. The first and the second period of time may have the same length or may have different lengths. The aforesaid period of time may be of from 1 day to several years, e.g. 10 years, preferably is of from 2 days to 1 year, more preferably is of from 1 week to 6 months, still more preferably is of from 2 weeks to 3 months. The period of time starts with inserting the transmucosal element in an implant site and ends with the removal thereof.

[0038] The term "subject", as used herein, relates to a vertebrate animal, preferably a mammal, more preferably a primate, most preferably a human. In some embodiments, the subject is a nonhuman animal. Preferably, the subject is a laboratory, livestock, or companion animal, such as a mouse, a rat, a guinea pig, a cow, a sheep, a pig, a dog, or a cat. Preferably, the subject has at least one dental implant, more preferably the subject suffers from peri-implant diseases or is at risk of suffering therefrom.

[0039] The improving of healing described herein comprises step (a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time.

[0040] The term "mounting" is understood by the skilled person. Preferably, the term includes any proceeding causing the transmucosal element to become removably fixed to the dental implant within an implant site, such that the transmucosal element at least partially contacts the periimplant mucosa of the implant site. Typically, the transmucosal element will be fixed to the transmucosal portion of the dental implant, i.e. preferably, at least a part of the contacts fixing the transmucosal element to the dental implant are made by the transmucosal portion. In principle, however, other methods of mounting the transmucosal element are envisaged, e.g. mounting via the enossal portion of the dental implant; such mounting may be preferred e.g. in cases of extensive resorption of bone and / or peri-implant mucosa, which may limits a contact or make a contact of the peri-implant mucosa to a transmucosal element mounted on a transmucosal portion of a dental implant impossible. At any rate, as detailed herein above, the transmucosal element is mounted such that it at least partially contacts the peri-implant mucosa of an implant site.

[0041] By mounting the transmucosal element on a dental implant as described, the healing improver is at least partially brought into contact with the peri-implant mucosa. Thus, the healing improver can exert its action on the peri-implant mucosa and the implant site in general. Thus, e.g. in case the healing improver is an attachment improver as described herein above, such contact may cause cells of the peri-implant mucosa to become attached to the transmucosal element, may cause cells of the peri-implant mucosa to undergo epigenetic changes e.g. increasing adherence of said cells to the transmucosal element, and / or may cause a basal lamina material to be deposited on the transmucosal element. Moreover, the transmucosal element, after mounting, may cause the peri-implant mucosa of the implant site to assume a predetermined shape and / or color.

[0042] The improving of healing described herein further comprises step (b) mounting a second removable transmucosal element onto said dental implant for a second time period. The second transmucosal element may, in principle, be mounted on top of the first transmucosal element. Preferably, however, the first transmucosal element is removed from the dental implant before mounting the second transmucosal element; thus, the second transmucosal element preferably replaces the first transmucosal element in step (b). It is, however, also envisaged that the first and the second transmucosal element are mounted concomitantly, e.g. as layered rings, and that in step (b), the second transmucosal element is made accessible by removing the first transmucosal element.

[0043] The improving of healing described herein further comprises step (c) improving healing of said dental implant, as specified herein above.

[0044] In view of the above, the skilled person understands that the transmucosal element including the healing improver may preferably be applied (i) during initial healing of an implant site, (ii) during restoration of an existing implant site, and / or (iii) as an intermediary measure to ameliorate or prevent deterioration of an implant site.

[0045] In initial healing, the transmucosal element including the healing improver may be applied during or after healing of the enossal portion into the jawbone, to prepare the implant site for mounting of a dental implant element comprising a transmucosal portion and / or for crown mounting. Thus, in such case, the transmucosal element including the healing improver may be applied to an apparently healthy implant site to accelerate healing and / or to prevent or to reduce inflammation or other deterioration of the implant site. In initial healing, the transmucosal element including the healing improver may, however, also be used to determine a suitable material for a transmucosal portion of a dental implant, e.g. to prevent peri-implant diseases; thus, the method may comprise compatibility testing of two or more materials in a subject, preferably in order to determine the material best suitable for the subject. In such case, the materials to be tested for compatibility, in particular the material identified to be best compatible, are / is the healing improver(s).

[0046] After insertion of the implant prosthesis, the transmucosal element including the healing improver may be applied to an already deteriorated implant site, preferably an implant site showing symptoms of peri-implant diseases such as inflammation, mucosal retraction, and / or bone resorption. In such case, the transmucosal element including the healing improver may in particular be used to prevent further deterioration and / or to induce healing of the implant site.

[0047] As an intermediary measure, the transmucosal element including the healing improver preferably is applied transiently, preferably after first symptoms of implant site deterioration were detected. Such treatment preferably includes treatment and / or prevention of risk factors and symptoms of beginning peri-implantitis, such as plaque and peri-implant mucositis.

[0048] Advantageously, it was found in the work underlying the present invention that by using removable transmucosal elements, implant sites can effectively restored without requiring changing dental implants or elements thereof. Also, transmucosal elements were found very suitable in compatibility testing, since they allow effective placement of a compound to be tested in direct contact with the peri-implant mucosa. In a preferred embodiment, the design of the removable transmucosal element allows removal together with the screw-retained implant restoration or after removing the implant restoration, without neither turning the removable transmucosal element nor requiring biopsy sampling. This non-invasive removal of the transmucosal element enables testing a mucosal tolerability on the elements' surface by analysing cell adherence with techniques such as qPCR assays and microscopy.

[0049] The definitions made above apply mutatis mutandis to the following. Additional definitions and explanations made further below also apply for all embodiments described in this specification mutatis mutandis.

[0050] The present invention also relates to a method for improving healing of a dental implant in a patient, said method comprising

[0051] (a) mounting a first removable transmucosal element comprising a first dental implant healing improver (healing improver) onto said dental implant for a first time period; (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby,

[0052] (c) improving healing of the dental implant.

[0053] The present invention further relates to a dental implant healing improver (healing improver) for use in improving care of an implant site of a subject comprising a dental implant, said improving care comprising

[0054] (A) mounting a first removable transmucosal element comprising said healing improver onto said dental implant, preferably onto a transmucosal portion thereof, for a first period of time;

[0055] (B) mounting a second removable transmucosal element comprising a further healing improver and / or not comprising said healing improver for a second time period;

[0056] (C) comparing an implant site status after the first period of time to an implant site status after the second period of time; and

[0057] (D) based on results of the comparing in step (C), deciding on further care of said implant site in said subject, thereby improving care.

[0058] The present invention also relates to a method of improving care of a dental implant in an implant site of a subject, said improving care comprising

[0059] (A) mounting a first removable transmucosal element comprising a dental implant healing improver (healing improver) onto said dental implant for a first period of time;

[0060] (B) mounting a second removable transmucosal element comprising a further healing improver and / or not comprising said healing improver for a second period of time;

[0061] (C) comparing an implant site status after the first period of time to an implant site status after the second period of time; and

[0062] (D) based on results of the comparing in step (C), deciding on further care of said implant site in said subject.

[0063] As referred to herein, the term "care" of an implant site includes any and all measures taken to maintain an implant site in a healthy state and / or to assist healing of an implant site. Thus, care preferably is treatment or prevention of disease as specified herein above and more preferably in particular includes measures for identifying and administering an effective and compatible healing improver to a subject, preferably adapted to a treatment situation. Thus, by means of the removable transmucosal elements described herein, two or more healing improvers may be compared in their effect on an implant site, or a healing improver may be compared to a control in the absence of the healing improver. As the skilled person will understand, the first and second period of time will be selected such that an effect of a healing improver may be visible, although advanced healing needs not necessarily have occurred; thus, the first and second period of time may be relatively short, e.g. of from 1 week to 3 months, preferably of from 2 weeks to one month.

[0064] Steps (A) and (B) are similar to steps (a) and (b) described herein above, thus the above applies mutatis mutandis. The improving care further comprises step (C) comparing an implant site status after the first period of time to an implant site status after the second period of time. Thus, in step (C), the status of an implant site after treatment with the healing improver is compared to the status after treatment in the absence of a healing improver or with a second healing improver, wherein the second healing improver is non-identical to the first healing improver.

[0065] The improving care further comprises step D) based on results of the comparing in step (C), deciding on further care of said implant site in said subject, thereby improving care. Thus, based on the comparing in step (C), it is possible to decide whether the healing improver of step (A) or the further healing improver or the absence of the healing improver in step (B) improved care for the implant site. Thus, either the one or the other will preferably be selected to include in further care. As the skilled person will understand in view of the description herein, in case it is found that including a healing improver improves care, said healing improver may be administered via a transmucosal element; the healing improver may, however, also be included in the dental implant, e.g. in a transmucosal portion of a dental implant.

[0066] The present invention also relates to a composition of matter for use in testing a mucosal tolerability of said composition of matter in a subject having at least one dental implant in an implant site, said method comprising

[0067] (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period;

[0068] (bb) examining the implant site after said time period; and, thereby,

[0069] (cc) testing said mucosal tolerability of said composition of matter.

[0070] Moreover, the present invention relates to a method for testing a mucosal tolerability of a composition of matter in a subject having at least one dental implant in an implant site, said method comprising (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period;

[0071] (bb) examining the implant site after said time period; and, thereby, (cc) testing said mucosal tolerability of said composition of matter.

[0072] The aforesaid methods may in particular comprise a further step of providing a subject having at least one dental implant in an implant site, said step preferably preceding step (aa).

[0073] The term "mucosal tolerability", as used herein, relates to the extent to which detectable adverse effects occur in a mucosa after contacting with a composition of matter. The mucosal tolerability is tested in an implant site, so the peri-implant mucosa is used as a model mucosa for testing purposes. Thus, mucosal tolerability is tested preferably to identify a suitable material for the manufacture of a dental implant, in particular its transmucosal portion and / or for the manufacture of a transmucosal element, or of a layer, preferably an outer layer, of the aforesaid dental implant or transmucosal element. Adverse effects which may occur if the mucosal tolerability of a composition of matter is low preferably include at least one symptom selected from the list consisting of reddening, pain, swelling, increased probing pocket depth, bleeding on probing, inflammation, suppuration, pus formation, mucosal retraction, and implant sheathing. In a preferred embodiment, a parameter indicative of cell adherence (e.g. adherence of fibroblasts, epithelial cells, and / or keratinocytes), and / or contact of basal lamina to the surface of the removable transmucosal element is used as an indicator of mucosal tolerability. Thus, in a preferred embodiment, a number, morphology, and / or shape of fibroblasts, a number of epithelial cells and / or keratinocytes and / or a measure of basal lamina deposition on the surface of the removable transmucosal element may be used as a surrogate marker of mucosal tolerability. As the skilled person will understand in view of the description herein, in a preferred embodiment, in case a transmucosal element with known low tolerability is used as a reference, higher cell numbers, increased spread-out fibroblast morphology, and / or larger amounts of basal lamina on the surface of the removable transmucosal element are indicative of good tolerability, while essentially equal or lower cell number, essentially equal or decreased spread-out fibroblast morphology, and / or essentially equal or lower amounts of basal lamina on the surface of the removable transmucosal element are indicative of low tolerability; also in a preferred embodiment, in case a transmucosal element with known good tolerability is used as a reference, lower cell numbers, decreased spread-out fibroblast morphology, and / or lower amounts of basal lamina on the surface of the removable transmucosal element are indicative of low tolerability, while essentially equal or higher cell numbers, essentially equal or increased spread-out fibroblast morphology and / or essentially equal or higher amounts of basal lamina on the surface of the removable transmucosal element are indicative of good tolerability.

[0074] In view of the above, the term "composition of matter" preferably includes any composition assumed to be mucosally tolerable or being of interest of being tested for mucosal tolerability. In accordance, the composition of matter may in particular be a candidate healing improver as specified herein above. The composition of matter may, however also be a candidate material for the production of a dental implant and / or a coating thereof, i.e. preferably is a candidate dental implant material.

[0075] The method of testing mucosal tolerability may be performed on a subject, in particular as a part of a treatment of an existing implant site containing a non-tolerated dental implant, i.e. a dental implant causing at least one of the adverse effects referred to herein above. Thus the method preferably leads to identification of a better tolerable composition of matter for use as a dental implant material or coating thereof. Preferably, in case such a composition of matter with better tolerability is identified, the method comprises a further step of replacing an existing dental implant by a dental implant consisting of or comprising, e.g. as a coating, the identified composition of matter. In such case, the method may contribute to healing of the implant site. In such case, the subject preferably is a human.

[0076] The method may, however, also be used for biocompatibility testing of candidate compositions of matter. In such case, the subject preferably is a laboratory animal, which is, more preferably sacrificed as the final step of the method.

[0077] The present invention also relates to a method of identifying an optimal design of a transmucosal portion of a dental implant, said method comprising

[0078] (AA) mounting a first removable transmucosal element having a first design onto said dental implant for a first time period,

[0079] (BB) mounting a second removable transmucosal element having a second design onto said dental implant for a second time period;

[0080] (CC) comparing implant site status after the first time period and after the second time period; and, (DD) identifying an optimal design of a transmucosal portion of a dental implant based on the results of comparison step (CC).

[0081] The term "design", as used herein, includes each and every property of a transmucosal portion of a dental implant which can be willfully influenced during production of the dental implant. Thus, a design of a transmucosal portion of a dental implant preferably is a composition, a coating, a surface roughness and / or a surface topography of said transmucosal portion. Appropriate candidate compositions of a transmucosal portion of a dental implant or a coating thereof are selected by the skilled person taking into account well-known criteria, in particular stability and principal biocompatibility. Surface roughness may be adjusted by surface treatment of the dental implant and / or by application of an appropriate coating. Similarly, surface topography may be adjusted according to known methods, e.g. nanoscale topography may be adjusted with nanotubes, nanopits and / or nanogrooves. Similar to the healing improvers referred to herein above, the optimal design may be identified using a transmucosal element, but the identified design may then also be included in the dental implant and in particular its transmucosal portion.

[0082] The term "optimal" design is used herein as a relative term; thus, while it may not be possible to identify the optimal design of all possible designs, it will usually be possible to identify the best design from a number of designs tested. Thus, the optimal design preferably is the best identified design and / or the preferred design for a dental implant. Also, the optimal design may be species specific, subspecies specific, population specific, subject specific, or even site specific. The criteria for identifying an optimal design essentially are same as for identifying a healing improver.

[0083] Furthermore, the instant invention relates to a kit comprising a dental implant and at least one removable transmucosal element, wherein said transmucosal element comprises a dental implant healing improver; and to a kit comprising at least two removable transmucosal elements mountable onto a dental implant, wherein a first of said removable transmucosal elements comprises a dental implant healing improver, and wherein a second of said removable transmucosal elements comprises a further healing improver and / or does not comprise said healing improver. In a preferred embodiment, the kit comprises a transmucosal portion of a dental implant and the aforesaid at least one removable transmucosal element. Thus, in a preferred embodiment, the kit comprises a one-piece dental implant, comprises an abutment including a transmucosal portion of a two-piece dental implant, or comprises a transmucosal portion of a three- or more piece dental implant, together with the aforesaid at least one removable transmucosal element.

[0084] The term “kit”, as used herein, refers to a collection of the aforementioned compounds or means. The components of the kit may be comprised by separate containers (i.e. as a kit of separate parts) or provided in a single container, e.g. as a composition as specified herein above. The kit preferably further comprises a housing, which preferably allows translocation of the components of the kit, in particular common translocation; thus, the housing may in particular be a transportable container comprising all specified components. Moreover, it is to be understood that the kit of the present invention may be used and preferably is adapted for practicing at least one of the methods referred to herein above. It is envisaged that all components may be provided in a ready-to-use manner for practicing a method referred to above. Further, the kit preferably contains instructions for carrying out said methods, e.g. dosage instructions. The instructions can be provided by a user manual on paper or electronic form. The kit preferably comprises further components, preferably a means for mounting and / or de-mounting of the transmucosal element, such as a forceps or tweezers adapted for handling the transmucosal element. Preferably, the kit comprises a multitude of non-identical transmucosal elements, wherein said transmucosal elements are non-identical in their composition and / or differ in at least one surface structure component. Thus, the kit preferably comprises a multitude of non-identical transmucosal elements, wherein said transmucosal elements differ in at least one constituent and / or coating component. In case the kit comprises a dental implant, the dental implant and the transmucosal element preferably are adapted such that the transmucosal element fits snugly onto the dental implant, in particular the transmucosal portion thereof. Preferably the kit is a kit for testing a mucosal tolerability of a composition of matter in a subject, and / or is a kit for personalized implant site treatment.

[0085] The present invention also relates to a use of a removable transmucosal element mountable onto a dental implant for improving implant healing in an implant site, wherein said transmucosal element comprises a healing improver.

[0086] The present invention further relates to a dental implant comprising a transmucosal portion and to a transmucosal element mountable onto a dental implant, wherein said transmucosal portion or transmucosal element comprises, preferably consists of, a silver-based alloy comprising gold, silver and copper. Preferably, said "silver-based alloy" comprises 7.5% (w / w) to 17.5% (w / w) gold, 40% (w / w) to 60% (w / w) silver, and 10% (w / w) to 20% (w / w) copper, plus optionally palladium, zinc and / or ruthenium, to a sum of 100% (w / w). More preferably, the silver-based alloy comprises 7.5% (w / w) to 17.5% (w / w) gold, 40% (w / w) to 60% (w / w) silver, 10% (w / w) to 20% (w / w) copper, 15% (w / w) to 20% (w / w) palladium, 0.1% (w / w) to 2% (w / w) zinc, and / or 0.01% (w / w) ruthenium to a sum of 100% (w / w). Still more preferably, the silverbased alloy comprises about 13% (w / w) gold, about 19% (w / w) palladium, about 54% (w / w) silver, about 14% (w / w) copper, about 0.7% (w / w) zinc and about 0.01% (w / w) ruthenium to a sum of 100% (w / w). Most preferably, the silver-based alloy essentially consists of 12.5% (w / w) gold, 18.9% (w / w) palladium, 53.65% (w / w) silver, 14.29% (w / w) copper, 0.65% (w / w) zinc, and 0.01% (w / w) ruthenium; thus, the alloy preferably is Pagalinor®2. In a preferred embodiment, the silver-based alloy comprising gold, silver and copper can be fabricated with high precision, provides surface stability under various conditions (e.g. temperature-, pH- changes), and / or enables filopodia spread of fibroblasts.

[0087] In view of the above, the following embodiments are particularly envisaged:

[0088] Embodiment 1 : A dental implant healing improver (healing improver) for use in improving healing of a dental implant in an implant site, wherein said improving healing comprises

[0089] (a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time;

[0090] (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby

[0091] (c) improving healing of said dental implant.

[0092] Embodiment 2: The healing improver of embodiment 1, wherein the second removable transmucosal element comprises a further healing improver and / or does not comprise said healing improver.

[0093] Embodiment 3 : The healing improver of embodiment 1 or 2, wherein the first removable transmucosal element and said second removable transmucosal element comprise the same healing improver.

[0094] Embodiment 4: The healing improver of embodiment 3, wherein the first removable transmucosal element and said second removable transmucosal element have the same composition. Embodiment s: The healing improver of embodiment 3 or 4, wherein said healing improver is unstable in the implant site.

[0095] Embodiment 6: A dental implant healing improver (healing improver) for use in improving care of an implant site of a subject comprising a dental implant, said improving care comprising

[0096] (A) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time;

[0097] (B) mounting a second removable transmucosal element comprising a further healing improver and / or not comprising said healing improver for a second time period;

[0098] (C) comparing an implant site status after the first period of time to an implant site status after the second period of time; and

[0099] (D) based on results of the comparing in step (C), deciding on further care of said implant site in said subject, thereby improving care.

[0100] Embodiment 7: A composition of matter for use in testing a mucosal tolerability of said composition of matter in a subject having at least one dental implant in an implant site, said method comprising

[0101] (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period;

[0102] (bb) examining the implant site after said time period; and, thereby,

[0103] (cc) testing said mucosal tolerability of said composition of matter.

[0104] Embodiment s: The composition of matter for use of embodiment 7, wherein said composition of matter is a candidate healing improver.

[0105] Embodiment 9: The composition of matter for use of embodiment 7, wherein said composition of matter is a candidate dental implant material.

[0106] Embodiment 10: The composition of matter for use of any one of embodiments 7 to 9, wherein said subject is a human or an experimental animal.

[0107] Embodiment 11 : A method for improving healing of a dental implant in a patient, said method comprising

[0108] (a) mounting a first removable transmucosal element comprising a first dental implant healing improver (healing improver) onto said dental implant for a first time period;

[0109] (b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby,

[0110] (c) improving healing of the dental implant. Embodiment 12: The method of embodiment 11, wherein the second removable transmucosal element comprises a further healing improver and / or does not comprise said healing improver.

[0111] Embodiment 13: The method of embodiment 11 or 12, wherein the first removable transmucosal element and said second removable transmucosal element comprise the same healing improver.

[0112] Embodiment 14: The method of embodiment 13, wherein the first removable transmucosal element and said second removable transmucosal element have the same composition.

[0113] Embodiment 15: The method of embodiment 13 or 14, wherein said healing improver is unstable in the implant site.

[0114] Embodiment 16: A method of improving care of a dental implant in an implant site of a subject, said improving care comprising

[0115] (A) mounting a first removable transmucosal element comprising a dental implant healing improver (healing improver) onto said dental implant for a first period of time;

[0116] (B) mounting a second removable transmucosal element comprising a further healing improver and / or not comprising said healing improver for a second period of time;

[0117] (C) comparing an implant site status after the first period of time to an implant site status after the second period of time; and

[0118] (D) based on results of the comparing in step (C), deciding on further care of said implant site in said subject.

[0119] Embodiment 17: A method for testing a mucosal tolerability of a composition of matter in a subject having at least one dental implant in an implant site, said method comprising (aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period;

[0120] (bb) examining the implant site after said time period; and, thereby,

[0121] (cc) testing said mucosal tolerability of said composition of matter.

[0122] Embodiment 18: The method of embodiment 17, wherein said subject is an experimental animal.

[0123] Embodiment 19: The method of embodiment 18, wherein said method comprises further step (ee) sacrificing said experimental animal.

[0124] Embodiment 20: A method of identifying an optimal design of a transmucosal portion of a dental implant, said method comprising

[0125] (AA) mounting a first removable transmucosal element having a first design onto said dental implant for a first time period, (BB) mounting a second removable transmucosal element having a second design onto said dental implant for a second time period;

[0126] (CC) comparing implant site status after the first time period and after the second time period; and,

[0127] (DD) identifying an optimal design of a transmucosal portion of a dental implant based on the results of comparison step (CC).

[0128] Embodiment 21 : The method of embodiment 20, wherein said design of a transmucosal portion of a dental implant is a composition, a coating, a surface roughness and / or a surface topography of said transmucosal portion.

[0129] Embodiment 22: A kit comprising a dental implant and at least one removable transmucosal element, wherein said transmucosal element comprises a dental implant healing improver.

[0130] Embodiment 23 : A kit comprising at least two removable transmucosal elements mountable onto a dental implant, wherein a first of said removable transmucosal elements comprises a dental implant healing improver, and wherein a second of said removable transmucosal elements comprises a further healing improver and / or does not comprise said healing improver.

[0131] Embodiment 24: The kit of embodiment 22 or 23, wherein said kit is a kit for testing a mucosal tolerability of a composition of matter in a subject.

[0132] Embodiment 25: The kit of any one of embodiments 21 to 24, wherein said kit is a kit for personalized implant site treatment.

[0133] Embodiment 26: Use of a removable transmucosal element mountable onto a dental implant for improving implant healing in an implant site, wherein said transmucosal element comprises a healing improver.

[0134] Embodiment 27: The subject matter of any one of embodiments 1 to 26, wherein said healing improver is selected from the list consisting of (i) a compound mediating cell adhesion, in particular of fibroblasts and junctional epithelial cells, (ii) a compound inducing epigenetic changes in cells contacting said healing improver, and / or (iii) a compound or composition of a surface of said removable transmucosal element inducing adhesion of a basal lamina.

[0135] Embodiment 28: The subject matter of any one of embodiments 1 to 27, wherein said healing improver is comprised in an extracellular matrix coating, a peptide coating, a polysaccharide coating, or metal coating.

[0136] Embodiment 29: The subject matter of embodiment 27, wherein said compound mediating cell adhesion is laminin, fibronectin, or nanoporous TiO2. Embodiment 30: The subject matter of embodiment 27, wherein said compound inducing epigenetic changes is silica, bioglass, graphene, or a biofunctionalized nanomaterial.

[0137] Embodiment 31 : The subject matter of embodiment 27, wherein said compound or composition of a surface is an alloy comprising a silver-based alloy comprising gold, silver and copper.

[0138] Embodiment 32: The subject matter of any one of embodiments 1 to 31, wherein said healing improver is not a biocide.

[0139] Embodiment 33: The subject matter of any of the preceding embodiments, wherein said healing improver is an attachment improver.

[0140] Embodiment 34: A dental implant attachment improver (attachment improver) for use in improving attachment of a peri-implant mucosa to a transmucosal portion of a dental implant in an implant site, wherein said improving attachment comprises

[0141] (A) mounting a removable transmucosal element comprising said attachment improver onto said dental implant for a period of time; and, thereby

[0142] (B) improving attachment of said peri-implant mucosa to said transmucosal portion of the dental implant in the implant site.

[0143] Embodiment 35: The subject matter of any one of embodiments 1 to 34, wherein said implant site is free of peri-implantitis.

[0144] Embodiment 36: A dental implant comprising a transmucosal portion or a transmucosal element mountable onto a dental implant, wherein said transmucosal portion or transmucosal element comprises, preferably consists of, a silver-based alloy comprising gold, silver and copper.

[0145] Embodiment 37: The dental implant or transmucosal element, wherein said silver-based alloy comprises 12.5% (w / w) gold, 18.9% (w / w) palladium, 53.65% (w / w) silver, 14.29% (w / w) copper, 0.65% (w / w) zinc, and 0.01% (w / w) ruthenium.

[0146] All references cited in this specification are herewith incorporated by reference with respect to their entire disclosure content and the disclosure content specifically mentioned in this specification.

[0147] Figure Legends Fig. 1 : (A) Schematic in situ representation of a two-piece dental implant 120 of the prior art, wherein the crown 124 and the transmucosal portion 122 are connected to the enossal component 126 via a screw thread; (B) side view of the enossal component 126 and the abutment component 134 of the two-piece dental implant of (A); (C) side view of a transmucosal element 140 of the invention, shaped as a conical ring; (D) cross-sectional view along axis A— A in (C).

[0148] Fig. 2: Schematic representations of exemplary embodiments of transmucosal elements 140 of the invention; (A) interlocking ring shape, the transmucosal element 140 fits snugly onto the transmucosal portion of the abutment component 134; (B) and (C) interlocking ring shapes with deviating outer geometry; the transmucosal element 140 of (B) broadens the proximal circumference of the transmucosal site; (C) as in (B), with the transmucosal element further extending onto the enossal component.

[0149] Fig. 3: Schematic representation of a mounting process of a transmucosal element 140 onto a two-piece dental implant; the transmucosal element 140 is mounted onto the transmucosal portion of the abutment component 134, which is then fixed into the enossal component 126; the transmucosal element 140 at least partially spans the mucosa 128 at the implant site.

[0150] The following Examples shall merely illustrate the invention. They shall not be construed, whatsoever, to limit the scope of the invention.

[0151] Example 1 (Fig. 1)

[0152] In a preferred embodiment, the transmucosal element 140 of the invention is mounted on a conventional dental implant 120 with restoration (crown) 124. As shown exemplarily in Fig. 1 A, B, the dental implant 120 may be a two-part implant comprising an enossal component 126 and an abutment component 134, wherein the abutment component 134 may be connected to the osseous, proximal implant element 126 by a screw thread. It is understood by the skilled person that the abutment component 134 of the dental implant 120 may be covered with a crown 124 to complete the tooth replacement. Preferably, only the portion of the dental implant 120 protruding into the oral cavity will be covered with a crown 124. Preferably, the transmucosal portion 122 of the dental implant 120 is comprised in the abutment component 134 in case the dental implant 120 is a two-part implant. However, also one-part dental implants 120 or multipart dental implants 120 are envisaged. In an embodiment, the inner surface of the transmucosal element 140 is designed to match the surface of the transmucosal portion 122 of the dental implant 120, in particular its abutment component 134 (Fig. 1 C, D), i.e. the transmucosal element preferably fits snugly onto the transmucosal portion 122. This way, the transmucosal element 140 can be removably mounted onto the transmucosal portion 122.

[0153] It may, however, also be envisaged that the inner surface of the transmucosal element 140 is structured to allow for some open space between the transmucosal portion 122 and the transmucosal element 140; e.g., the transmucosal element 140 may comprise grooves parallel to the longitudinal axis of the dental implant 120. Such a configuration may e.g. be used to provide the possibility to apply medication towards the bone 130.

[0154] Example 2 (Fig. 2)

[0155] As shown in Fig. 2, the transmucosal element 140 may have any shape deemed appropriate by the skilled person for the intended purpose. E.g., the transmucosal element 140 may have a conical shape, e.g. in correspondence to the outer surface of the transmucosal portion 122 of the dental implant 120 (Fig. 2A). In such case, the mucosa at the implant site will essentially follow the contour of the transmucosal portion 122, with a small increase in diameter caused by the transmucosal element 140.

[0156] Alternatively, the transmucosal element 140 may also at least partially deviate from the form of the transmucosal portion 122 (Fig. 2B, C). As will be appreciated, the transmucosal element 140 of Fig. 2B causes a displacement of the mucosa from the proximal portion of the transmucosal portion 122, or prevents growth of mucosa into said proximal section in the first place. The transmucosal element 140 of Fig. 2C may e.g. be used in case it is desirable to additionally extend the transmucosal element 140 onto the enossal implant portion.

[0157] Example 3 (Fig. 3)

[0158] As shown in Fig. 3, in the exemplary case of a two-part dental implant 120, the transmucosal element 140 may be mounted by unscrewing the abutment component 134 from the enossal component 126, placing the transmucosal element 140 onto the transmucosal portion 122 of the abutment component 134, and re-inserting the abutment component 134 into the enossal component 126. Literature

[0159] Atieh et al. (2013), J Periodontol 84: 1586

[0160] Berglundh et al, (2011), J Clin Periodontol 38 Suppl 11 : 188

[0161] Chantier et al. (2023), Clin Oral Implants Res 34 Suppl 26: 64 Derksen et al. (2023), Clin Oral Implants Res 34 Suppl 26: 104

[0162] Ferraris et al. (2017), Materials Science Engineering C76: 1

[0163] Larsson et al. (2018), J Biomed Mater Res B Appl Biomater 106(5):2065

[0164] WO 2015 / 158825 Al

[0165] List of reference numbers

[0166] 120 dental implant 122 transmucosal portion

[0167] 124 restoration (crown)

[0168] 126 enossal component

[0169] 128 mucosa (gingiva)

[0170] 130 bone 132 retainer portion

[0171] 134 abutment component

[0172] 140 transmucosal element

Claims

Claims1. A dental implant healing improver (healing improver) for use in improving healing of a dental implant in an implant site, wherein said improving healing comprises(a) mounting a first removable transmucosal element comprising said healing improver onto said dental implant for a first period of time;(b) mounting a second removable transmucosal element onto said dental implant for a second time period; and, thereby(c) improving healing of said dental implant.

2. The healing improver for use of claim 1, wherein the second removable transmucosal element comprises a further healing improver and / or does not comprise said healing improver.

3. The healing improver for use of claim 1 or 2, wherein the first removable transmucosal element and said second removable transmucosal element comprise the same healing improver.

4. The healing improver for use of any one of claims 1 to 3, wherein said healing improver is selected from the list consisting of (i) a compound mediating cell adhesion, (ii) a compound inducing epigenetic changes in cells contacting said healing improver, and / or (iii) a compound or composition of a surface of said removable transmucosal element inducing adhesion of a basal lamina.

5. The healing improver for use of claim 4, wherein said compound mediating cell adhesion is laminin, fibronectin, or nanoporous TiCh; wherein said compound inducing epigenetic changes is silica, bioglass, graphene, or a biofunctionalized nanomaterial; and / or wherein said compound or composition of a surface is a silver-based alloy comprising gold, silver and copper.

6. The healing improver for use of any one of claims 1 to 5, wherein the silver-based alloy comprises about 13% (w / w) gold, about 19% (w / w) palladium, about 54% (w / w) silver, about 14% (w / w) copper, about 0.7% (w / w) zinc, and about 0.01% (w / w) ruthenium to a sum of 100% (w / w), preferably comprises 12.5% (w / w) gold, 18.9% (w / w) palladium,53.65% (w / w) silver, 14.29% (w / w) copper, 0.65% (w / w) zinc, and 0.01% (w / w) ruthenium.

7. The healing improver for use of anyone of claims 1 to 6, wherein said healing improver is comprised in an extracellular matrix coating, a peptide coating, a polysaccharide coating, or metal coating.

8. The healing improver of any one of claims 1 to 7, wherein said healing improver is an attachment improver.

9. A method for testing a mucosal tolerability of a composition of matter in a subject having at least one dental implant in an implant site, said method comprising(aa) mounting a removable transmucosal element comprising or consisting of said composition of matter onto said dental implant for a time period;(bb) examining the implant site after said time period; and, thereby,(cc) testing said mucosal tolerability of said composition of matter, wherein said subject is an experimental animal and wherein said method comprises further step (dd) sacrificing said experimental animal.

10. The method of claim 9, wherein said composition of matter is a candidate healing improver and / or is a candidate dental implant material.

11. A kit comprising at least two removable transmucosal elements mountable onto a dental implant, wherein a first of said removable transmucosal elements comprises a dental implant healing improver, and wherein a second of said removable transmucosal elements comprises a further healing improver and / or does not comprise said healing improver.

12. The kit of claim 11, wherein said kit is a kit for testing a mucosal tolerability of a composition of matter in a subject.

13. The subject matter of any one of claims 1 to 12, wherein said healing improver is not a biocide.

14. The subject matter of any one of claims 1 to 13, wherein said implant site is free of peri- implantitis, preferably is free of a peri-implant disease.

15. The subject matter of any one of claims 1 to 14, wherein the dental implant and the removable transmucosal element are configured for a push-to-fit or a snap-to fit type of mounting.

16. A dental implant comprising a transmucosal portion or a transmucosal element mountable onto a dental implant, wherein said transmucosal portion or transmucosal element comprises, preferably consists of, a silver-based alloy comprising about 13%(w / w) gold, about 19% (w / w) palladium, about 54% (w / w) silver, about 14% (w / w) copper, about 0.7% (w / w) zinc, and about 0.01% (w / w) ruthenium to a sum of 100% (w / w), preferably comprises 12.5% (w / w) gold, 18.9% (w / w) palladium, 53.65% (w / w) silver, 14.29% (w / w) copper, 0.65% (w / w) zinc, and 0.01% (w / w) ruthenium.

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